Coordination Funds

协调基金

• 批准号: 454008509
• 负责人: Professor Dr. Benedikt Bertold Kaufer, Ph.D.
• 金额: --
• 依托单位: Institut für Virologie (WE05)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/454008509?language=en
• 关键词: Coordination; Funds

The chicken has a long history as a model organism and many seminal discoveries were made in this species. In the context of immunology, for example B cells were first discovered as antibody producing cells in chickens and graft versus host disease was identified in chicken embryos. In addition, poultry is one of the most important protein sources in the human diet worldwide. A plethora of pathogens infect chickens and threaten animal welfare and food safety. To protect the animals from these diseases, chickens receive many vaccines and are considered the most vaccinated species on earth; however, the underlying immune responses remain largely unknown.The objective of this research unit is to provide a better understanding of the avian immune system. To achieve this, we will focus on the adaptive immune response and its interactions with the most relevant pathogens. We will dissect the chicken immune response using recently generated genetically modified chickens lacking critical immune cells in combination with important infection models. This includes B cell, αβ T cell and γδ T cell knockout chickens as well as Salmonella, Infectious bursal disease virus (IBDV), Marek Disease Virus (MDV), and different protozoa species including Eimeria spp.. Simultaneously, we will characterize regulatory T cells by using the recently discovered chicken FOXP3 as a marker and further investigate the role of natural killer cells in birds. In addition, we will use for the first time immunopeptidomics approaches to identify peptides from pathogen presented by the chicken major histocompatibility complex (MHC) using our recently developed B and T cell culture systems upon infection with MDV and IBDV. Beyond this, we will develop adoptive transfer approaches using knockout chickens and a novel next generation sequencing-based MHC genotyping system to dissect the immune responses upon vaccination and subsequent pathogen challenges. This will allow us to identify and characterize the cell populations that provide protection against important pathogens. Taken together, the unique expertise of the research unit members, novel genetically modified chickens, infection models and state-of-the-art immunological tools is an exceptional combination that will contribute the success of the proposed work and will provide important insights into the avian immune system.

鸡作为模式生物有很长的历史，在这个物种中有许多开创性的发现。例如，在免疫学的背景下，首先在鸡中发现了B细胞作为抗体产生细胞，并在鸡胚中发现了移植物抗宿主病。此外，家禽是全世界人类饮食中最重要的蛋白质来源之一。大量病原体感染鸡，威胁动物福利和食品安全。为了保护动物免受这些疾病的侵袭，鸡接种了许多疫苗，被认为是地球上接种疫苗最多的物种；然而，潜在的免疫反应在很大程度上仍不清楚。本研究单位的目的是更好地了解鸟类的免疫系统。为了实现这一点，我们将重点研究适应性免疫反应及其与最相关病原体的相互作用。我们将使用最近产生的缺乏关键免疫细胞的转基因鸡结合重要的感染模型来剖析鸡的免疫反应。这包括B细胞、αβT细胞和γδT细胞敲除鸡以及沙门氏菌、传染性法氏囊病病毒、马立克病病毒和包括艾美耳球虫在内的不同原生动物物种。同时，我们将利用最近发现的鸡FOXP3作为标志物来表征调节性T细胞，并进一步研究自然杀伤细胞在鸟类中的作用。此外，我们将首次使用免疫表位学方法，在感染MDV和IBDV后，使用我们最近开发的B和T细胞培养系统，从鸡主要组织相容性复合体(MHC)呈递的病原体中鉴定多肽。除此之外，我们将开发使用基因敲除鸡的采用转移方法和新的基于测序的新一代MHC基因分型系统，以分析疫苗接种和后续病原体挑战时的免疫反应。这将使我们能够识别和表征提供对重要病原体的保护的细胞群。总而言之，研究单位成员的独特专业知识、新型转基因鸡、感染模型和最先进的免疫学工具是一个特殊的组合，将有助于拟议工作的成功，并将为鸟类免疫系统提供重要的见解。